title: Absence of polo-like kinase 3 in mice stabilizes Cdc25A after DNA damage but is not sufficient to produce tumors.
abstract: The polo-like kinases (Plks1-5) are emerging as an important class of proteins involved in many facets of cell cycle regulation and response to DNA damage and stress. Here we show that Plk3 phosphorylates the key cell cycle protein phosphatase Cdc25A on two serine residues in its cyclinB/cdk1 docking domain and regulates its stability in response to DNA damage. We generated a Plk3 knock-out mouse and show that Cdc25A protein from Plk3-deficient cells is less susceptible to DNA damage-mediated degradation than cells with functional Plk3. We also show that absence of Plk3 correlates with loss of the G1/S cell cycle checkpoint. However, neither this compromised DNA damage checkpoint nor reduced susceptibility to proteasome-mediated degradation after DNA damage translated into a significant increase in tumor incidence in the Plk3-deficient mice.
authors.affiliation: Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0524, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Myer
authors.forename: Susan B
authors.initials: SB
authors.lastname: Robbins
authors.forename: Moying
authors.initials: M
authors.lastname: Yin
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Boivin
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Greis
authors.forename: El Mustapha
authors.initials: el M
authors.lastname: Bahassi
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stambrook
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D004249:DNA Damage; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D054875:Ubiquitination; D020687:cdc25 Phosphatases / Q000737:chemistry / Q000378:metabolism*
chemical_list: C093328:Plk3 protein, mouse; D017346:Protein Serine-Threonine Kinases; D020687:cdc25 Phosphatases